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Front Immunol. 2011; 2: 54.
Published online Nov 8, 2011. doi:  10.3389/fimmu.2011.00054
PMCID: PMC3342372
Primary Immunodeficiency Diseases: An Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency
Waleed Al-Herz,1,2 Aziz Bousfiha,3 Jean-Laurent Casanova,4,5 Helen Chapel,6 Mary Ellen Conley,7,8* Charlotte Cunningham-Rundles,9 Amos Etzioni,10 Alain Fischer,11 Jose Luis Franco,12 Raif S. Geha,13 Lennart Hammarström,14 Shigeaki Nonoyama,15 Luigi Daniele Notarangelo,13,16* Hans Dieter Ochs,17 Jennifer M. Puck,18 Chaim M. Roifman,19 Reinhard Seger,20 and Mimi L. K. Tang21,22,23
1Department of Pediatrics, Kuwait University, Kuwait City, Kuwait
2Allergy and Clinical Immunology Unit, Department of Pediatrics, Al-Sabah Hospital, Kuwait City, Kuwait
3Clinical Immunology Unit, Casablanca Children Hospital Ibn Rochd Medical School, King Hassan II University, Casablanca, Morocco
4St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA
5Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Necker Medical School, University Paris Descartes and INSERM U980, Paris, France
6Clinical Immunology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK
7Department of Pediatrics, University of Tennessee College of Medicine, Memphis, TN, USA
8Department of Immunology, St. Jude Children’s Research Hospital, Memphis, TN, USA
9Department of Medicine and Pediatrics, Mount Sinai School of Medicine, New York, NY, USA
10Meyer’s Children Hospital – Technion, Haifa, Israel
11Pediatric Hematology-Immunology Unit, Hôpital Necker Enfants-Malades, Assistance Publique–Hôpital de Paris, Necker Medical School, Paris Descartes University, Paris, France
12Group of Primary Immunodeficiencies, University of Antioquia, Medellín, Colombia
13Division of Immunology, Children’s Hospital Boston, Boston, MA, USA
14Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden
15Department of Pediatrics, National Defense Medical College, Saitama, Japan
16The Manton Center for Orphan Disease Research, Children’s Hospital Boston, Boston, MA, USA
17Department of Pediatrics, University of Washington and Seattle Children’s Research Institute, Seattle, WA, USA
18Department of Pediatrics, University of California San Francisco and UCSF Benioff Children’s Hospital, San Francisco, CA, USA
19Division of Immunology and Allergy, Department of Pediatrics, The Hospital for Sick Children and the University of Toronto, Toronto, ON, Canada
20Division of Immunology, University Children’s Hospital, Zürich, Switzerland
21Department of Allergy and Immunology, Royal Children’s Hospital Melbourne, Melbourne, VIC, Australia
22Murdoch Childrens Research Institute, Melbourne, Melbourne, VIC, Australia
23Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia
Edited by: Eric Meffre, Yale University School of Medicine, USA
Reviewed by: Eric Meffre, Yale University School of Medicine, USA
*Correspondence: Mary Ellen Conley, Department of Pediatrics, University of Tennessee College of Medicine, Memphis, TN, USA; Department of Immunology MS 351, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA. e-mail: maryellen.conley/at/stjude.org; Luigi Daniele Notarangelo, Division of Immunology and The Manton Center for Orphan Disease Research, Children’s Hospital Boston, Karp Research Building, Room 20217, 1 Blackfan Circle, Boston, MA 02115, USA. e-mail: luigi.notarangelo/at/childrens.harvard.edu
This article was submitted to Frontiers in Primary Immunodeficiencies, a specialty of Frontiers in Immunology.
Received August 25, 2011; Accepted September 20, 2011.
Abstract
We report the updated classification of primary immunodeficiency diseases, compiled by the ad hoc Expert Committee of the International Union of Immunological Societies. As compared to the previous edition, more than 15 novel disease entities have been added in the updated version. For each disorders, the key clinical and laboratory features are provided. This updated classification is meant to help in the diagnostic approach to patients with these diseases.
Keywords: primary immunodeficiency diseases
The International Union of Immunological Societies (IUIS) Expert Committee on Primary Immunodeficiency met in New York City, May 31–June 1, 2011 to update the classification of human primary immunodeficiencies (PIDs). Novel developments in gene discovery and increased knowledge in the mechanisms that govern immune system development and function have resulted in the identification of several novel PIDs in the last 2 years.
The classification of primary immunodeficiencies (PIDs) provides a framework to help in the diagnostic approach to patients. As in recent classifications, eight major groups of PIDs have been included in the Tables; however the order of the Tables has been changed with Table Table22 now describing the “Well-defined syndromes with immunodeficiency” (previously Table Table3)3) to reflect the immunological similarity between the disorders included in this Table and those in Table Table1,1, “Combined immunodeficiencies.”
Table 2
Table 2
Well-defined syndromes with immunodeficiency.
Table 3
Table 3
Predominantly antibody deficiencies.
Table 1
Table 1
Combined immunodeficiencies.
Table 4
Table 4
Diseases of immune dysregulation.
Any classification of human disorders is somewhat arbitrary, and the classification of PIDs is no exception. Some disorders might well belong to more than one group. CD40 ligand deficiency, for example, is reported both in Tables Tables11 and and33 (“Predominantly antibody deficiencies”), to reflect the facts that failed B cell isotype switching was historically the most prominent feature of this condition (originally named Hyper-IgM syndrome) and that some patients survive into adulthood without significant opportunistic infections and do well with only immunoglobulin replacement therapy. Explanatory notes provided after each Table offer additional information (particularly where a condition appears in more than one Table) and indicate which new disorders have been added to that Table.
Although this updated classification reports on the most typical immunological findings and associated clinical and genetic features for the various PIDs, there is extensive clinical, immunological, and molecular heterogeneity that can not be easily recapitulated in a brief summary. To facilitate a more rigorous analysis of each disease, a column has been added on the right with a hyperlink to refer to its catalog number in the Online Mendelian Inheritance in Man (OMIM) publicly accessible database (www.omim.org) of human genetic disorders. It is suggested that the reader consult this regularly updated and fully referenced resource.
The prevalence of the various PIDs varies in different countries. For this reason, in this new classification, we have elected to avoid giving a comment on the relative frequency of PID disorders. However, an asterisk has been placed in the first column, after the disease name, to identify disorders for which fewer than 10 unrelated cases have been reported in the literature. Some of these forms of PID can be considered extremely rare. Others have only recently been identified and it may be that more patients will be detected over time.
Finally, it is increasingly recognized that different mutations in the same gene may result in different phenotypes and may be associated with different patterns of inheritance. This concept of clinical, immunological, and genetic heterogeneity is assuming foremost importance. Notes in the text or in the footnotes identify such heterogeneity, when known.
The scope of the IUIS Expert Committee on Primary Immunodeficiency is to increase awareness, facilitate recognition, and promote optimal treatment for patients with Primary Immunodeficiency disorders worldwide. For this reason, in addition to periodically revising the Classification of PIDs, the Expert Committee is also actively involved in the development of diagnostic criteria and in providing, upon request, advice with regard to therapeutic guidelines.
Table 5
Table 5
Congenital defects of phagocyte number, function, or both.
Table 6
Table 6
Defects in innate immunity.
Table 7
Table 7
Autoinflammatory disorders.
Table 8
Table 8
Complement deficiencies.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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